The objective of this proposal is to enable investigators at Children's National Medical Center (CNMC) to actively pursue investigations of the therapy, biology, and causes of malignant disease in infants, children and adolescents through participation in the Childrens Cancer Group (CCG). Investigators from CNMC will provide scientific and administrative leadership of such activities. CNMC will enter all eligible patients from the Institution and encourage entry of all eligible patients from its affiliate network on Group-wide studies of multi-modality therapy of acute leukemia and solid tumors. CNMC will continue to develop and participate in limited institution pilot (toxicity and/or feasibility) studies incorporating novel therapeutic strategies for CNS preventive therapy in childhood ALL, and dose-intensified treatment plans which incorporate the adjuvant use of hematopoietic growth factors. CNMC will develop and participate in limited Institution pilot studies of new agents and novel therapeutic approaches in the management of brain tumors, and will participate in a regional collaborative group in clinical trials which pose questions of CNS pharmacologic interests. CNMC will continue as one of the most active CCG participants in the investigation of new agents, including cytotoxic as well as biologic agents in the Phase I and Phase II setting. CNMC will comply with protocol-specified therapy as well as required evaluations and will submit complete and accurate data to the Operations Office in a timely fashion and actively participate in biologic studies and clinical pharmacology studies. CNMC will expand its CCG ALL Biology Reference Laboratory activity in the identification of prospective patients for biotherapeutic studies incorporating monoclonal antibodies to leukemia cell associated antigens and the investigation of enhancement of the cytotoxicity of such antibodies. Correlative laboratory studies of the significance of the expression of the mdr-1 gene at diagnosis and relapse and correlation with clinical outcome will continue in homogeneously treated patient groups. Molecular genetic markers, specifically immunoglobulin, T-cell receptor, and the SIL-SCL rearrangement will be utilized as markers of minimal residual disease prior to and following the delayed intensification phases of therapy and correlated with treatment outcome. CNMC will investigate the biological significance of shad tumor gangliosides and continue studies of the correlation between serum GD2 and outcome in neuroblastoma. CNMC will participate in case controlled epidemiologic studies of childhood cancer to investigate the possible relationship between genetic predisposition and pre and post-natal environmental factors on the development of malignancy. As the outcome for children with cancer has improved, CNMC investigators will participate in the formulation and execution of Group-wide studies to examine the long term impact of successful anti-cancer therapy on aspects of growth and development.